Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Dec 23, 2008 - Jul 06, 2009
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: For this endpoint supporting data for a main most critical degradation product are provided. The relevant study was performed according to GLP and the methods applied are fully compliant with OECD TG 402.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline

Test animals

Species:
rat
Strain:
other: CRL:CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Limited, Manston Road. Margate, Kent, UK
- Age at study initiation: group 1: appr. 8 weeks; group 2: appr. 8-9 weeks
- Weight at study initiation: group 1: 227-250 g (m), 176-190 g (f); group 2: 182-190 g and 213-243 g (f)
- Fasting period before study: overnight before dosing
- Housing: groups of3 in polypropylene cages
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21 °C
- Humidity (%): 33 - 80 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: day 1 To: day 15

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 7 x 8 cm
- % coverage: 100
- Type of wrap if used: gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution):
- Constant volume or concentration used: according to body weight
- For solids, paste formed: no
Duration of exposure:
24 h
Doses:
2000 mg/(kg bw
No. of animals per sex per dose:
2000 mg/kg bw: 5 (m), 5 (f)
2000 mg/kg bw: 5 (f)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: days: 1, 8, 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
No formal stati stical analysis was conducted.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were 2 unscheduled deaths. One female was found dead on Day 2, approximately 19 1/2 h after dosing. The animal had shown no signs of reaction to treatment before death and there was no indication that its death resulted from the dosing procedure.
Another female from the additional females treated was euthanised approximately 3 1/4 h after dosing because of adverse signs of reaction to treatment.
Clinical signs:
The female that was euthan ised displayed subdued behaviour, piloerection, red nasal and ocular discharge, wetness around the genital area and was cold to the touch from approximately 3 h after dosing.
In the surviving animals there was no evidence of systemic toxicity with adverse signs restricted to findings at the dorsal surface. Reddening was seen in males and females from Day 2, and flaking skin was recorded in females from Day 3. In addition, dry scabbing was recorded in 2 females from Day 5. These signs had resolved in all males by Day 4 and in all surviving females by Day 10.
Body weight:
Body weights and body weight gains were considered to be acceptable for rats of th is age and
strain.
Gross pathology:
The female found dead had red staining to the dorsum. This is considered to be evidence of erythema caused by the test item. The animal that was euthanised
had discolouring of the dorsal skin, which is also considered to be a result of test item application. The in-life finding of wetness around the genital area was also evident.
There were other find ings that are not untypical of background findings in rats of this strain and age on these study types, and, therefore they are considered not to be indicative of an effect of treatmenl. These included a mottled appearance of the kidneys of 2 males and enlarged mandibular lymph nodes in one female. The decedent had a dilated uterus.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The median dermal lethal dose (LD50) is greater than 2000 mg/kg bw.
Executive summary:

Study Design

The study investigated the dennal toxicity potential of N-butylpyridinium chloride after a single administration to Sprague-Dawley rats. Five males and 5 females received N-butylpyridinium chloride at 2000 mg/kg bw. The test item was administered as supplied onto the water moistened clipped dorsal trunk and covered with a water moistened occlusive patch for 24 h. This study was performed according to GLP and the methods applied are fully compliant with OECD TG 402.

Results

All 5 males survived treatment. One female was found dead on Day 2, approximately 19h after dosing, and, consequently. a second group of 5 females received N-butylpyridinium chloride at 2000 mg/kg bw. One of these females was euthanised approximately 3h after dosing because of adverse signs. All animals were observed for adverse signs up to 14 days after dosing and all animals received a gross necropsy.
The female found dead on Day 2 had shown no signs of reaction to treatment before death and there was no ind ication that its death resulted from the dosing procedure. Necropsy findings revealed that the dorsal skin was stained red. The female that was euthanised approximately 3h after dosing displayed subdued behaviour, piloerection, red nasal and ocular discharge, wetness around the genital area and was cold to the touch. Necropsy findings revealed red staining or discolouration to the dorsum and wetness around the genital area.
Among the males and the surviving females there were no other systemic signs recorded and only local findings at the site of test item application were noted. These included erythema, reddening of the dorsal surface, flaking skin and dry scabbing. These signs had resolved by Day 10.
Body weight gains were considered to be acceptable for rats of this age and strain and there were no necropsy findings in the surviving animals that were considered to be related to treatment.

Conclusion

Under the conditions of the study, a topical dosage of 2000 mg/kg bw of N-butylpyridinium chloride to Sprague-Dawley rats resulted in the unscheduled death of 2 of 15 animals and caused local irritation at the treatment site. It is considered that the median dermal lethal dose (LD50) is greater than 2000 mg/kg bw.